Study of XmAb942 in Healthy Participants and Participants With Ulcerative Colitis

A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study in Healthy Participants Followed by a Randomized, Double-Blind, Placebo-Controlled Phase 2 Study in Participants With Moderate-To-Severe Active Ulcerative Colitis.

The Phase 1 study described herein will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of XmAb942 in healthy volunteers (Parts A and B). Part C of this study will be a Phase 2 study to evaluate XmAb942 in participants with ulcerative colitis (UC).

This study consists of 3 parts, as follows:

Part A: Single ascending dose (SAD) in healthy participants, will entail administration of XmAb942 or matching placebo at 3 different dose levels of XmAb942.

Part B: Multiple ascending dosing for up to 3 doses, will entail administration of XmAb942 or matching placebo at 2 different dose levels of XmAb942.

Part C: Participants with moderately to severely active UC to receive 3 different dose levels of XmAb942 or placebo during a 12-week induction period and single dose level of XmAb942 during a 40-week maintenance period, followed by a 24 week follow-up period.

Inclusion Criteria:

Parts A and B

• Age 18-55
• Must be in good health with no significant medical history
• Clinical laboratory values within normal range
• BMI 18-35 (inclusive)
• Contraceptive use by men or women consistent with local regulations
• Able and willing to provide written informed consent

Part C

• Age 18-75
• Must be in good health with no significant medical history
• UC diagnosis ≥ 3 months prior to screening
• Diagnosis of moderately to severely active UC as defined by a (MMS) ≥ 5, with a MES ≥ 2 and RBS ≥ 1
• Evidence of UC extending ≥ 15 cm from the anal verge, as determined by screening colonoscopy
• Must have inadequate response to, loss of response to, or intolerance to at least 1 of the conventional or advanced therapies of UC
• Able and willing to provide written informed consent

Exclusion Criteria:

Parts A and B

• Any physical or psychological condition that prohibits study completion
• History of suicidal behavior or suicidal ideation
• Heavy use of nicotine containing products
• HIV, hepatitis B and hepatitis C positive
• Cardiac arrhythmia, or clinically significant abnormal ECG
• Active use of prescription medications within 14 days of Day -1
• Active use of over-the-counter, or herbal medication within 7 days of Screening
• Other investigational products within 30 days
• Blood or plasma donation within 60 days
• Pregnant or breastfeeding

Part C

• Any physical or psychological condition that prohibits study participation
• Diagnosis of Crohn disease, indeterminate colitis, indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, and diverticular disease associated with colitis.
• Positive screen for Clostridium difficile (C. Difficile) toxins
• HIV, hepatitis B and hepatitis C positive
• Cardiac arrhythmia, or clinically significant abnormal ECG
• Pregnant or breastfeeding

Other protocol defined inclusion/exclusion criteria apply.